Antianginal and myocardial metabolic properties of verapamil in coronary artery disease

To determine the metabolic cost of administering an experimental calcium antagonist, verapamil, to patients with coronary artery disease, 12 such patients were studied at rest and during stress with atrial pacing before and after intravenous treatment with verapamil (bolus dose of 0.1 mg/kg body weight, followed by infusion at 0.005 mg/kg per min). The mean (±standard deviation) aortic pressure at rest (98 ± 22 mg Hg), coronary sinus blood flow (88 ± 17 ml/min) and myocardial oxygen consumption (10.7 ± 2.4 ml O₂/min) decreased to 88 ± 20 mm Hg (p < 0.0004), 77 ± 14 ml/min (p < 0.03) and 8.8 ± 2.5 ml O₂/min (p < 0.01), respectively, after administration of verapamil. With atrial pacing, these values were 105 ± 25 mm Hg, 151 ± 50 ml/min and 18.5 ± 6.4 ml O₂/min, respectively, before infusion of verapamil, and then decreased to 87 ± 14 mm Hg (p < 0.006), 107 ± 31 ml/min (p < 0.0002) and 13.3 ± 4.4 ml O₂/min (p < 0.001) during infusion. Angina occurred in all patients with atrial pacing before verapamil (threshold to pain: 93 ± 67 seconds). After verapamil, the threshold to pain in six patients increased to 191 ± 183 seconds; and no pain was experienced by the remaining six (p < 0.0005). Before administration of verapamil lactate extraction decreased from 24 ± 9 to 10 ± 11 percent (p < 0.0002) during atrial pacing, and 9 (75 percent) of the 12 patients exhibited electrocardiographic S-T segment depressions. After administration of verapamil lactate extraction normalized to 22 ± 9 percent during atrial pacing, and the electrocardiogram reverted to baseline in all but one patient. These findings indicate that verapamil decreases left ventricular myocardial metabolic demands, and concomitantly greatly increases the threshold to angina.